Long-term changes in synaptic strength are thought to represent a cellular correlate of learning and memory. In the hippocampus, long-term potentiation (LTP) and long-term depression (LTD) have been studied extensively, and a number of different mechanisms have been elucidated, some of which coexist at the same synapses. In the striatum, changes in synaptic function are thought to correlate with behaviors such as habit formation, as well as with pathologies such as Parkinson's and Huntington's disease and drug addiction. However, the mechanisms, or even the types of plasticities present at these synapses, have not been fully described. The goal of this research proposal is to examine LTD in both the dorsal striatum and its ventral extension, the nucleus accumbens. A number of studies have found various and conflicting results regarding LTD in these areas. To examine the types of LTD present at synapses in both dorsal striatum and nucleus accumbens, various induction protocols and experimental paradigms will be tested. Specific mechanisms of LTD induction and expression will then be studied using electrophysioiogical recordings combined with molecular techniques such as viral-mediated gene transfer. These studies will provide a framework for understanding how long-term changes in synaptic strength in the striatum are related to such health issues as addiction and neurodegenerative disease.